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【结 构 式】 
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【药物名称】HU-308 【化学名称】1-[4(R)-[4-(1,1-Dimethylheptyl)-2,6-dimethoxyphenyl]-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl]methanol 【CA登记号】 【 分 子 式 】C27H42O3 【 分 子 量 】414.63399 |
【开发单位】Hebrew University (Originator), University of Aberdeen (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Non-Opioid Analgesics, Cannabinoid CB2 Agonists |
合成路线1
Esterification of (1S,5R)-myrtenol (I) with pivalyl chloride (II) yields ester (III), which is then oxidized with Na2CrO4 in HOAc-Ac2O to give 4-oxo-myrtenyl pivalate (IV). Reduction of (IV) with lithium tri-t-butoxyaluminohydride in THF affords 4-hydroxymyrtenyl pivalate (V), which is then condensed with 5-(1,1-dimethylheptyl)resorcinol (VI) in the presence of p-TsOH in CH2Cl2 to furnish compound (VII). Treatment of (VII) with K2CO3 in MeOH provides methyl ether derivative (VIII), which is finally reduced with LiAlH4.
| 【1】 Mechoulam, R.; et al.; Synthesis of the individual, pharmacologically distinct, enantiomers of a tetrahydrocannabinol derivative. Tetrahedron Asymmetry 1990, 1, 5, 315. |
| 【2】 Goldenberg, D.; Horowitz, M.; Hanus, L.; Breuer, A.; Ross, R.A.; Pertwee, R.G.; Mechoulam, R.; Shiloah, S.; Tchilibon, S.; Fride, E.; HU - 308: A specific agonist for CB2, a peripheral cannabinoid receptor. Proc Natl Acad Sci USA 1999, 96(25): 14228 1999, 96, 25, 14228. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 44155 | (6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methanol | 515-00-4 | C10H16O | 详情 | 详情 |
| (II) | 13597 | 2,2-Dimethylpropanoyl chloride; Pivaloyl chloride | 3282-30-2 | C5H9ClO | 详情 | 详情 |
| (III) | 44156 | (6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methyl pivalate | C15H24O2 | 详情 | 详情 | |
| (IV) | 44157 | (6,6-dimethyl-4-oxobicyclo[3.1.1]hept-2-en-2-yl)methyl pivalate | C15H22O3 | 详情 | 详情 | |
| (V) | 44158 | [(4R)-4-hydroxy-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl]methyl pivalate | C15H24O3 | 详情 | 详情 | |
| (VI) | 20233 | 5-(1,1-dimethylheptyl)-1,3-benzenediol | C15H24O2 | 详情 | 详情 | |
| (VII) | 44159 | [(4R)-4-[4-(1,1-dimethylheptyl)-2,6-dihydroxyphenyl]-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl]methyl pivalate | C30H46O4 | 详情 | 详情 | |
| (VIII) | 44160 | [(4R)-4-[4-(1,1-dimethylheptyl)-2,6-dimethoxyphenyl]-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl]methyl pivalate | C32H50O4 | 详情 | 详情 |